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L71F mutation in rat cardiac troponin T augments crossbridge recruitment and detachment dynamics against α-myosin heavy chain, but not against β-myosin heavy chain
- Source :
- Journal of Muscle Research and Cell Motility. 37:215-223
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- The N-terminal extension of human cardiac troponin T (TnT), which modulates myofilament Ca2+ sensitivity, contains several hypertrophic cardiomyopathy (HCM)-causing mutations including S69F. However, the functional consequence of S69F mutation is unknown. The human analog of S69F in rat TnT is L71F (TnTL71F). Because the functional consequences due to structural changes in the N-terminal extension are influenced by the type of myosin heavy chain (MHC) isoform, we hypothesized that the TnTL71F-mediated effect would be differently modulated by α- and β-MHC isoforms. TnTL71F and wild-type rat TnT were reconstituted into de-membranated muscle fibers from normal (α-MHC) and propylthiouracil-treated rat hearts (β-MHC) to measure steady-state and dynamic contractile parameters. The magnitude of the TnTL71F-mediated attenuation of Ca2+-activated maximal tension was greater in α- than in β-MHC fibers. For example, TnTL71F attenuated maximal tension by 31% in α-MHC fibers but only by 10% in β-MHC fibers. Furthermore, TnTL71F reduced myofilament Ca2+ sensitivity by 0.11 pCa units in α-MHC fibers but only by 0.05 pCa units in β-MHC fibers. TnTL71F augmented rate constants of crossbridge recruitment and crossbridge detachment dynamics in α-MHC fibers but not in β-MHC fibers. Collectively, our data demonstrate that TnTL71F induces greater contractile deficits against α-MHC than against β-MHC background.
- Subjects :
- Male
0301 basic medicine
Gene isoform
Myofilament
medicine.medical_specialty
Physiology
chemical and pharmacologic phenomena
Major histocompatibility complex
medicine.disease_cause
Biochemistry
Rats, Sprague-Dawley
Ventricular Myosins
03 medical and health sciences
Myofibrils
Troponin T
CrossBridge
Internal medicine
Myosin
medicine
Animals
Protein Isoforms
Mutation
Myosin Heavy Chains
biology
Chemistry
Hypertrophic cardiomyopathy
Cell Biology
medicine.disease
Myocardial Contraction
Rats
030104 developmental biology
biology.protein
Biophysics
Cardiology
Calcium
Subjects
Details
- ISSN :
- 15732657 and 01424319
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Journal of Muscle Research and Cell Motility
- Accession number :
- edsair.doi.dedup.....89fbb9824b936946c4d06eb1abc7b3f5